The Scientific Core will exist to provide reagents and services to the various projects within this program project grant and the Neuropathology Core. In many cases the need for specific reagents and services will be common to multiple projects, thus providing them centrally through a focused and skilled staff will be the most efficient method of operation. The reagents and services to be provided will include the following: DNA sequencing of sporadic CJD patients recruited for the clinical trial to confirm that they have no pathogenic mutations in their PrP genes; purification and isolation of the stereoisomers of quinacrine; analytical chemistry for characterization of new chemical compounds; large scale cell-based assays for initial screening of new compounds from combinatorial synthesis and from rational drug design studies; determination of the metabolism and pharmacokinetics of quinacrine in both humans and mice; determination of the metabolism and pharmacokinetics of other lead compounds that emerge from either of the medicinal chemistry projects; synthesis of radiolabeled drug analogs and the determination of the bioavailability of drugs in brain tissue; interaction analysis by surface plasmon resonance (Biacore); purified infectious prions for assaying potential drugs; 13C and 15N-labeled recombinant proteins for NMR studies of PrP carrying a dominant-negative mutation or the P101 L mutation; antibodies for histology and cell-based studies. This core will be directed by two senior scientists who between them have extensive experience of prion research, analytical chemistry, protein chemistry, molecular biology, immunology, antibody production, recombinant protein technology, and development of automated assays. They will supervise a group of scientific research associates who will carry out the functions listed above.